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Biomedical subjects

J E Hall

Publications and source records attributed to J E Hall.

At least 343 records · Page 19Linked to original sources

Pentastomid nymph from the brain of a squirrel monkey (Saimiri sciureus). II. Morphology of the host response.

A Porocephalus nymph found in the meninges of a squirrel monkey was encapsulated by connective tissue cells and fibrils presumably derived from the pia mater. The capsule was composed of an inner layer (IL) adjacent to the nymphal integument and an outer layer (OL) adherent to the brain surface. Separating the two layers was a capsular space. The IL was lined by a granular material adjacent to the nymph surface and possessed impressions of annulae and the apical pits of chloride cells. The surface of IL facing the capsular space was characterized by a monolayer of cells possessing extensive anastomosing plasmalemmal processes. The OL was composed of several tiers of fibroblasts and associated collagen fibrils that adhered to the brain surface in the form of a thickened pia mater. It is suggested that the capsule was formed by a modification of the pia that isolated the nymph and created an "intracapsular space" with specialized lining cells to facilitate fluid exchange.

Animals↗

Increased urinary excretion of aromatic amino acid catabolites by Microtus montanus chronically infected with Trypanosoma brucei gambiense.

Microtus montanus infected with Trypanosoma brucei gambiense for 16 and 21 days excreted significantly greater quantities of several aromatic amino acid catabolites when compared to uninfected control animals. Very large quantities of three aromatic alpha-keto acids (alpha-oxocarboxylic acids), phenylpyruvic acid, 4- hydroxyphenylpyruvic acid and indole-3-pyruvic acid, were excreted by infected animals. Increased excretion of indole-3-lactic acid and indole-3-acetic acid was also detected. Gas chromatographic-mass spectral analysis of the trimethylsilyl derivatives of phenylpyruvic acid, 4- hydroxyphenylpyruvic acid and indole-3-pyruvic acid confirms the identity of the aromatic alpha-keto acids elevated during infection. The marked alpha-keto aciduria indicates that a large disturbance exists in aromatic amino acid metabolism in this chronic animal model of African trypanosomiasis. The disturbance may contribute to the pathogenesis of the disease. The increased catabolite concentrations may also prove to be useful diagnostically and prognostically.

Amino Acids↗

Thickness dependence of monoglyceride bilayer membrane conductance.

We have studied the conductance properties of unmodified monoglyceride membranes as a function of monoglyceride chain length. As membrane thickness decreases from 31 to 20 nm, the steepness of the current-voltage (I-V) curve increases from 80 mV per e-fold current increase to 52 mV per e-fold current increase. The zero-voltage conductance increases more than 1,000-fold and the apparent activation energy of conductance decreases from 18.4 to 14.2 kcal/mol. We have analyzed our results using both the Nernst-Planck equation and absolute rate theory. Both approaches are consistent with our results and give consistent values for the parameters describing the I-V curves. We conclude that both the surface ion concentration and the distance from the surface of the membrane at which the energy of an ion rises appreciably above its value in solution (position of the barrier) are invariant with thickness.

Electric Conductivity↗

Alamethicin. A rich model for channel behavior.

Alamethicin, a 20-amino acid peptide, has been studied for a number of years as a model for voltage-gated channels. Recently both the x-ray structure of alamethicin in crystal and an NMR solution structure have been published (Fox and Richards, 1982. Bannerjee et al., 1983). Both structures show that the amino end of the molecule forms a stable alpha-helix nine or 10 residues in length and that the COOH-terminal ends exhibits a variable hydrogen bonding pattern. We have used synthetic analogues of alamethicin to test various hypotheses of its mode of action. As a result of these studies we propose a channel structure in which the COOH-terminal residues bond together as a beta-barrel, leaving the alpha- helices free to rotate under the influence of the electric field and gate the channel. Though the number of monomers per channel varies with experimental conditions, the gating charge per monomer stays close to that expected from an alpha-helical gate. We can also alter the sign of the voltage which turns on a channel by varying the charge on the alamethicin analogue. Channels are always slightly cation-selective even though formed by monomers with negative, positive, or zero formal charge. Channels are less stable in low ionic strength solutions than high. Finally, alamethicin conductance parameters vary systematically with changes in membrane thickness. We show how these results and others in the literature can be explained by a fairly detailed structural model. The model can be easily generalized to a form more suited to high molecular weight single-peptide-chain proteins.

Alamethicin↗

The pathogenic role of the kidney.

The discussions of this article suggest that the pressure natriuresis mechanism of the kidneys is the most important of all long-term regulators of arterial pressure. This is especially so because of the infinite-gain feature of this mechanism, a feature that is explained here. However, experiments have shown that it is not the accumulation of sodium per se in the body that causes hypertension. Instead, it is the increase in extracellular fluid volume that usually accompanies sodium accumulation that increases the arterial pressure. If the increase in fluid volume is prevented, hypertension will not occur despite marked sodium retention. Long-term autoregulation in hypertension plays a very important role for two major reasons: (a) it greatly increases the total peripheral resistance when the cardiac output increases only a small amount, and (b) when it promotes arteriolar constriction, capillary pressure is reduced, which in turns allows a very large proportion of the extracellular fluid to remain in the blood rather than to leak into the interstitium. Marked loss of renal mass usually does not cause hypertension because, as long as there is a proper balance between glomerular filtration capability and tubular reabsorption capability, as little as 10% of the normal kidney mass theoretically can excrete the normal daily load of salt without a significant rise in arterial pressure. However, whenever the ratio of glomerular filtration capability to tubular reabsorption capability falls below normal, salt and water are retained until enough hypertension develops to overcome the deficit in glomerular filtration.

Adaptation, Physiological↗

Mechanisms of escape from sodium retention during angiotensin II hypertension.

This study examined the role of increased renal arterial pressure (RAP) in renal escape from the chronic Na-retaining effects of angiotensin II (ANG II). When RAP was allowed to increase during ANG II infusion (5 ng X kg-1 X min-1), urinary Na excretion (UNaV) decreased transiently on the first day but there was no significant change in Na iothalamate space or cumulative Na balance when ANG II infusion was continued for 6 days. Mean arterial pressure (MAP) rose from 100 +/- 3 to 132 +/- 2 mmHg after 3 days and remained near that level for the next 5 days of ANG II infusion. When RAP was prevented from rising with a servo-controlled aortic occluder, UNaV remained below control even after 6 days of ANG II infusion, cumulative Na balance increased by 210 +/- 37 meq, and Na iothalamate space rose by 1,158 +/- 244 ml. MAP did not plateau when RAP was servo-controlled during ANG II infusion but continued to rise and after 6 days averaged 157 +/- 3 mmHg. In three of the eight dogs in which RAP was servo-controlled during ANG II infusion, Na and water retention became so severe that MAP increased to 165-180 mmHg and pulmonary edema developed within 4-6 days. These data suggest that a rise in RAP is essential in allowing the kidneys to escape from the chronic Na-retaining actions of ANG II and in attaining Na balance and a stable level of MAP without severe volume expansion.

Aldosterone↗

Control of glomerular filtration rate: role of intrarenally formed angiotensin II.

This study was designed to investigate the role of intrarenally formed angiotensin II (ANG II) in controlling glomerular filtration rate (GFR) during reduction of renal artery pressure (RAP). The experimental design prevented renin released by the kidney from entering the systemic circulation and therefore prevented changes in circulating ANG II from influencing GFR control. In dogs with only a functional intrarenal renin-angiotensin system (RAS), GFR and renal blood flow (RBF) were not significantly altered by RAP reduction to 70 mmHg. After blockade of intrarenal ANG II formation with SQ 14225, reduction of RAP to 70 mmHg decreased GFR and filtration fraction to 75.6 +/- 7.0 and 59.0 +/- 4.1% of control, respectively, while RBF remained at 129.3 +/- 8.8% of control. Calculated efferent arteriolar resistance decreased considerably more when RAP was reduced after SQ 14225, whereas preglomerular resistance decreased to about the same level as observed prior to SQ 14225 infusion. After return of endogenously produced ANG II by recirculation of the renal venous blood or after infusion of ANG II (following SQ 14225) at a rate that restored RBF to the control level (with RAP held at 70 mmHg in each case), GFR, filtration fraction, and calculated efferent resistance were restored to control levels, but preglomerular resistance did not change. These results suggest that intrarenal ANG II formation plays an important role in maintaining GFR during reductions in RAP by constricting efferent arterioles.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

Supracondylar fracture of the humerus in children. Further experience with a study in orthopaedic decision-making.

In a study of the results of each therapeutic act in the treatment program of displaced supracondylar fractures of the humerus, 108 consecutive children were analyzed. An initial attempt at closed reduction was noted in 101 cases, with the attempt successful in 61. Of these elbows, 19 were flexed at least 120 degrees following reduction, with all 19 maintaining reduction. Twenty-two of the remaining reduced fractures were splinted in less than 120 degrees of flexion; 19 lost reduction. Traction alone, via olecranon pin or skin, was unsuccessful in achieving reduction and unreliable in maintaining reduction once achieved. Crossed Kirschner wires, placed percutaneously or under direct visualization, were uniformly successful in maintaining reduction. From these data an algorithm has been constructed to facilitate objective decision-making in the treatment of this challenging fracture.

Adolescent↗

Angiotensin II natriuresis and anti-natriuresis: role of renal artery pressure in anaesthetized dogs.

The aim of this study was to determine the role of changes in renal artery pressure (RAP), renal haemodynamics, and tubular reabsorption in mediating the natriuretic and anti-natriuretic actions of angiotensin II (ANG II). In anaesthetized dogs, endogenous ANG II formation was blocked with SQ-14225 and ANG II was infused intravenously at rates of 5-1215 ng/kg/min while RAP was either servo-controlled at the normal level or permitted to increase. When RAP was servo-controlled to prevent a rise in RAP, ANG II infusion at all rates from 5-1215 ng/kg/min decreased urinary sodium excretion (INaV) and fractional sodium excretion (FENa), while increasing fractional reabsorption of lithium (FRLi), an index of proximal tubule fractional sodium reabsorption (FRDNa). When RAP was permitted to increase, ANG II infusion rates up to 45 ng/kg/min decreased UNaV, and FENam while increasing FRLi and FRDNa greater than However, at 135 ng/kg/min and above UNaV and FENE increased while FRLi and FRDNa decreased when RAP was allowed to rise, even though renal blood flow and filtration fraction were not substantially different from the values observed when RAP was servo-controlled. Filtered sodium load was slightly higher when RAP was permitted to increase during ANG II infusion, compared to the dogs in which RAP was servo-controlled, although the differences were not statistically significant. Thus, even very large doses of ANG II cause anti-natriuresis when RAP is prevented from increasing. The natriuretic effect of high doses of ANG II is caused by increased RAP which decreases fractional sodium reabsorption in proximal and distal tubules and causes slight increase in sodium delivery to the tubules.

Absorption↗

13C nuclear magnetic resonance studies of anaerobic glycolysis in Trypanosoma brucei spp.

Anaerobic glycolysis in Trypanosoma brucei spp. has been studied by 13C NMR at 50 and 75.5 MHz. The uptake of [U-13C]glucose by cell suspensions of T. b. brucei was monitored by time-course spectroscopy, and while no anomeric specificity was found, the end-products of glycolysis were confirmed as glycerol and pyruvate together with alanine and dihydroxypropionate. The intermediacy of L-glycerol-3-phosphate was also ascertained. The incorporation of C-1 of [1-13C]glucose and of C-6 of [6-13C]glucose into glycerol and pyruvate in T. b. gambiense was quantified by measurement of the longitudinal relaxation times of the species involved. An incorporation to the extent of 66% of each substrate into equimolar amounts of glycerol and pyruvate indicate that Keq for the triosephosphate-isomerase-mediated reaction approaches unity.

Anaerobiosis↗

Pressure effects on alamethicin conductance in bilayer membranes.

We report here the first observations of the effects of elevated hydrostatic pressure on the kinetics of bilayer membrane conductance induced by the pore-forming antibiotic, alamethicin. Bacterial phosphatidylethanolamine-squalene bilayer membranes were formed by the apposition of lipid monolayers in a vessel capable of sustaining hydrostatic pressures in the range, 0.1-100 MPa (1-1,000 atm). Principal observations were (a) the lifetimes of discrete conductance states were lengthened with increasing pressure, (b) both the onset and decay of alamethicin conductance accompanying application and removal of supra-threshold voltage pulses were slowed with increasing pressure, (c) the onset of alamethicin conductance at elevated pressure became distinctly sigmoidal, suggesting an electrically silent intermediate state of channel assembly, (d) the magnitudes of the discrete conductance levels observed did not change with pressure, and, (e) the voltage threshold for the onset of alamethicin conductance was not altered by pressure. Apparent activation volumes for both the formation and decay of conducting states were positive and of comparable magnitude, namely, approximately 100 A3/event. Observation d indicates that channel geometry and the kinetics of ion transport through open channels were not affected by pressure in the range employed. The remaining observations indicate that, while the relative positions of free-energy minima characterizing individual conducting states at a given voltage were not modified by pressure, the heights of intervening potential maxima were increased by its application.

Alamethicin↗

Alamethicin-induced current-voltage curve asymmetry in lipid bilayers.

We have examined the causes of the asymmetry of the current-voltage curve induced by addition of alamethicin to one side of a black lipid membrane. We find that the alamethicin-induced current-voltage (I-V) curve has an inherent asymmetry. If it were possible to confine all alamethicin molecules to one side of the membrane, the I-V curve would exhibit a positive branch (voltage being measured with respect to the side of the membrane trans to the alamethicin addition) of steeper logarithmic slope than the negative branch and at a lower absolute value of potential. This condition is not usually realized, however, because alamethicin can leak through the membrane, so that, except at very high alamethicin concentrations and in certain kinds of membranes, the positive branch of the current-voltage curve has the same logarithmic slope as the negative branch and appears to arise from alamethicin which diffuses from the cis to the trans side of the membrane. We develop simple quantitative models for these two cases.

Alamethicin↗

Renal hemodynamic actions of angiotensin II: interaction with tubuloglomerular feedback.

The present study was designed to investigate the importance of interactions between angiotensin II (ANG II) and other intrinsic control mechanisms, including tubuloglomerular feedback (TGF), in controlling renal hemodynamics. When endogenous ANG II formation was blocked by SQ 14225 infusion and changes in myogenic activity were minimized by servo controlling renal arterial pressure, ANG II infusion (20 ng . kg-1 . min-1 iv) did not change glomerular filtration rate but decreased renal blood flow (RBF) from 286 +/- 36 to 179 +/- 31 ml/min due to increases in calculated preglomerular (54%) and efferent (100%) arteriolar resistances. After inhibition of TGF by occluding the ureter during mannitol diuresis, ANG II infusion (20 ng . kg-1 . min-1) decreased RBF from 229 +/- 25 to 151 +/- 19 ml/min while increasing glomerular hydrostatic pressure (calculated from ureteral stop-flow pressure and plasma colloid osmotic pressure) from 56.7 +/- 2.5 to 62.3 +/- 2.2 mmHg. Postglomerular resistance increased to 173 +/- 17% of control, but preglomerular resistance did not change significantly during ANG II infusion after inhibition of TGF. These data suggest that the direct renal vasoconstrictor action of ANG II is confined mainly to postglomerular vessels and that changes in preglomerular resistance that occur when ANG II levels are inappropriately elevated in normal animals are caused by other intrinsic control mechanisms, such as TGF.

Angiotensin II↗

Acute and chronic servo-control of renal perfusion pressure.

We describe a servo-control system for acute and chronic regulation of renal perfusion pressure or pressures in other parts of the circulation. The system employs a Dacron-reinforced inflatable silastic occluder of sufficient strength and durability to produce large pressure gradients for long periods of time (at least 10 days) in the abdominal aortas of large dogs. The occluder is inflated with an inexpensive, bidirectional DC motor syringe pump that is controlled by a comparator feedback circuit connected to the output of a driver amplifier of a Grass polygraph or any other suitable recorder. The system has a rapid response time for precise control and has been used to maintain a constant renal perfusion pressure in experiments lasting as long as 10 days. The system has diverse applications in studies of acute or chronic regulation of renal hemodynamics as well as the hemodynamics of other organ systems. The main advantages of this system, besides its durability and precision of control, are that it is very inexpensive (total cost including the syringe pump is less than $150), easy to construct, and can be used in chronic studies for servo-controlling renal perfusion pressure or pressures in other parts of the circulation.

Animals↗